Randomized Clinical Trial of Real-Time fMRI Amygdala Neurofeedback for Major Depressive Disorder: Effects on Symptoms and Autobiographical Memory Recall

Abstract

Objective Patients with depression show blunted amygdala hemodynamic activity to positive stimuli, including autobiographical memories. The authors examined the therapeutic efficacy of real-time functional MRI neurofeedback (rtfMRI-nf) training aimed at increasing the amygdala’s he-modynamic response to positive memories in patients with depression. Method In a double-blind, placebo-controlled, randomized clinical trial, unmedicated adults with depression (N=36) were randomly assigned to receive two sessions of rtfMRI-nf either from the amygdala (N=19) or from a parietal control region not involved in emotional processing (N=17). Clinical scores and autobiographical memory performance were assessed at baseline and 1 week after the final rtfMRI-nf session. The primary outcome measure was change in score on the Montgomery-Åsberg Depression Rating Scale (MADRS), and the main analytic approach consisted of a linear mixed-model analysis. Results In participants in the experimental group, the hemo-dynamic response in the amygdala increased relative to their own baseline and to the control group. Twelve participants in the amygdala rtfMRI-nf group, compared with only two in the control group, had a >50% decrease in MADRS score. Six participants in the experimental group, compared with one in the control group, met conventional criteria for remission at study end, resulting in a number needed to treat of 4. In participants receiving amygdala rtfMRI-nf, the percent of positive specific memories recalled increased relative to baseline and to the control group. Conclusions rtfMRI-nf training to increase the amygdala hemo-dynamic response to positive memories significantly decreased depressive symptoms and increased the percent of specific memories recalled on an autobiographical memory test. These data support a role of the amygdala in recovery from depression.

Advances in fMRI Real-Time Neurofeedback

“…While it is argued that placebo-controlled and double-blinded trials on fMRI neurofeedback are needed to confirm clinical effects [68], recent studies have started to document the significant clinical effects of neurofeedback with just these kinds of studies design [21,69]. …”

Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety

“…Within this context, the emergence of real-time functional magnetic resonance imaging neurofeedback (rt-fMRI NF) training (NFT) approaches that allow subjects to gain volitional control over regional brain activity have been considered as a putatively promising strategy [28-30]. Importantly, previous studies have confirmed this potential of rt-fMRI NF by demonstrating that training success in terms of control over regional activity can be maintained beyond the training session [31-34], and that training-induced neural activity changes can modulate emotional experience in healthy subjects [31] and patients with major depression [32-35]. …”

“…Initial studies have begun to evaluate the therapeutic potential of rt-fMRI NF in clinical populations and demonstrated that upregulating activity in primary emotion-processing regions such as the insula and amygdala can successfully decrease symptoms in patients with major depression [32-34]. Given the critical role of the amygdala in anxiety and consistently observed hyperresponsivity in this region in anxiety-related disorders [18, 36, 37], previous rt-fMRI NF studies trained subjects to downregulate neural activity in this region and demonstrated that this strategy has the potential to enhance ER and attenuate anxious arousal [38-41].…”

Real-Time Functional Magnetic Resonance Imaging Amygdala Neurofeedback Changes Positive Information Processing in Major Depressive Disorder

“…In a pilot study using this intervention, individuals with MDD successfully increased their amygdala hemodynamic response during positive memory recall, and this increase was associated with improvements in state-dependent measures of mood(25). In the first randomized double-blind clinical trial of amygdala rtfMRI-nf for MDD we found two rtfMRI-nf sessions resulted in large and significant clinical improvements relative both to baseline and a control group receiving rtfMRI-nf from a parietal region putatively not involved in emotion processing(26). …”

“…The current study, conducted as a secondary analysis on data from a clinical trial of neurofeedback that has already been published(26), tested the specificity and generalizability of the intervention by examining the effects of rtfMRI-nf training on tasks of emotional processing known to be affected by antidepressant treatments–the backward masking task(BMT) and the Emotional Test Battery(ETB). Testing generalizability and specificity is a critical step for determining the clinical potential of this procedure(27).…”